A study was undertaken to determine whether effectors of anchorage-independent growth (AIG) were present in the amniotic fluid and/or the placenta of human and subhuman primates. Assays depended on the ability of positive effectors to induce soft agar colony formation in a clone of normal rat kidney cells (NRK-49F), while negative effectors inhibited the spontaneous soft agar colony formation of a clone of human melanoma cells (A375 Ag5). It was determined that while acid/alcohol extraction of term placenta yielded a large quantity of several size classes of both positive and negative effectors of AIG, in organ cultures of first trimester human placenta, only a single 20,000 M.W. negative effector was secreted to the serum-free conditioned medium. Also, in both human (first trimester) and monkey (term) amniotic fluid, a low activity, 8,000 M.W. positive effector was detected, while inhibitors of AIG exhibited considerable variability, perhaps related to gestational age. The discovery of these effectors in the feto-placental unit encourages speculation that they play a role in embryology.